The compound 2-chloro-9-[3'-(N'-2-hydroxyethylpiperazino-N)-propylidene]-thiaxanthene has for some years, in the form of a mixture of the cis-trans isomers, proved a valuable neuroleptic drug in the treatment of psychotic disorders, mostly schizophrenic patients.
The compound, which in the following is called clopenthixol (CPT) for short, is effective in doses of from about 5 mg to about 25 mg per unit dosage. Clopenthixol is preferably used in the form of acid addition salts, such as the dihydrochloride, in oral unit dosage forms. When clopenthixol is prepared according to the method described in U.S. Pat. No. 3,116,291 a mixture of isomers is obtained wherein approximately 35%, mostly about 30-50%, of the most active isomer (for convenience called alpha-clopenthixol) is present.
A separation of the isomers along the lines described in U.S. Pat. No. 3,116,291 failed to succeed. When fractional crystallization of either the free base or an acid addition salt thereof in various solvents was attempted the inactive beta-isomer being the most insoluble always crystallized out first, and from the mother liquors resulting from the crystallizations only mixtures of the alpha- and beta-isomers were obtained.